Abstract

Endothelin receptors (ET_A and ET_B) mediate responses to ET-1. ET_B receptor function seems to differ between a similarly sized arterial and venous pair, the rat vena cava (RVC) and rat thoracic aorta (RA). ET_B receptors mediate RVC contraction directly, but it is unclear whether ET_B receptors mediate contraction in RA. Because of these apparent differences in ET_B receptor-mediated vascular contraction, we hypothesize that relaxant ET_B-receptor mechanisms in RVC would be different from those in RA. RA and RVC rings were isolated from rats for measurement of isometric contraction. When contracted with prostaglandin F-2α (PGF-2α) (20 μM), the ET_B receptor agonist sarafotoxin-6c (S6c) (100 nM) significantly relaxed RA and RVC. N^ω-Nitro-l-arginine (LNNA) (100 μM) or endothelial denudation abolished relaxation to S6c in RA. By contrast, S6c-induced relaxation of RVC was attenuated but not abolished by LNNA and endothelial denudation. RVC (PGF-2α-contracted) relaxed to low concentrations of ET-1, whereas under the same conditions RA responded with contraction. ET-1-induced relaxation in RA was observed only with ET_A receptor blockade. Vessels from dopamine-β-hydroxylase-ET_B transgenic rats, which lack functional ET_B receptors in the vasculature, were also used. RVC (PGF-2α-contracted) from these rats did not relax to ET-1. Thus, although both RA and RVC possess endothelial relaxant ET_B receptors, RA and RVC differ in that relaxant ET_B receptors may also be present in smooth muscle of RVC. Moreover, the mechanisms of endothelial cell ET_B receptor-mediated relaxation in RA and RVC are not the same.